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Paired mesoderm homeobox protein 2B (Neuroblastoma Phox) (NBPhox) (PHOX2B homeodomain protein) (Paired-like homeobox 2B)

 PHX2B_HUMAN             Reviewed;         314 AA.
Q99453; Q6PJD9;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
17-OCT-2006, sequence version 2.
22-NOV-2017, entry version 164.
RecName: Full=Paired mesoderm homeobox protein 2B;
AltName: Full=Neuroblastoma Phox;
Short=NBPhox;
AltName: Full=PHOX2B homeodomain protein;
AltName: Full=Paired-like homeobox 2B;
Name=PHOX2B; Synonyms=PMX2B;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Neuroblastoma;
PubMed=9039501; DOI=10.1093/dnares/3.5.311;
Yokoyama M., Nishi Y., Yoshii J., Okubo K., Matsubara K.;
"Identification and cloning of neuroblastoma-specific and nerve
tissue-specific genes through compiled expression profiles.";
DNA Res. 3:311-320(1996).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=11034547; DOI=10.1089/104454900439773;
Adachi M., Browne D., Lewis E.J.;
"Paired-like homeodomain proteins Phox2a/Arix and Phox2b/NBPhox have
similar genetic organization and independently regulate dopamine beta-
hydroxylase gene transcription.";
DNA Cell Biol. 19:539-554(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=10395798; DOI=10.1006/geno.1999.5845;
Yokoyama M., Watanabe H., Nakamura M.;
"Genomic structure and functional characterization of NBPhox (PMX2B),
a homeodomain protein specific to catecholaminergic cells that is
involved in second messenger-mediated transcriptional activation.";
Genomics 59:40-50(1999).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
VARIANT CCHS ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-241 INS, AND
VARIANTS 254-ALA--ALA-258 DEL AND 255-ALA--ALA-259 DEL.
PubMed=14566559; DOI=10.1007/s00439-003-1036-z;
Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H.,
Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W.,
Nakamura T., Hayasaka K.;
"Molecular analysis of congenital central hypoventilation syndrome.";
Hum. Genet. 114:22-26(2003).
[6]
INVOLVEMENT IN CCHS, AND TRIPLET REPEAT EXPANSION.
PubMed=12640453; DOI=10.1038/ng1130;
Amiel J., Laudier B., Attie-Bitach T., Trang H., de Pontual L.,
Gener B., Trochet D., Etchevers H., Ray P., Simonneau M., Vekemans M.,
Munnich A., Gaultier C., Lyonnet S.;
"Polyalanine expansion and frameshift mutations of the paired-like
homeobox gene PHOX2B in congenital central hypoventilation syndrome.";
Nat. Genet. 33:459-461(2003).
[7]
VARIANTS LEU-100 AND GLY-141, AND POSSIBLE INVOLVEMENT IN NBLST2.
PubMed=15024693; DOI=10.1086/383253;
Trochet D., Bourdeaut F., Janoueix-Lerosey I., Deville A.,
de Pontual L., Schleiermacher G., Coze C., Philip N., Frebourg T.,
Munnich A., Lyonnet S., Delattre O., Amiel J.;
"Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in
neuroblastoma.";
Am. J. Hum. Genet. 74:761-764(2004).
[8]
VARIANTS CCHS GLN-141 AND ARG-143, AND TRIPLET REPEAT EXPANSION.
PubMed=15657873; DOI=10.1086/428366;
Trochet D., O'Brien L.M., Gozal D., Trang H., Nordenskjoeld A.,
Laudier B., Svensson P.-J., Uhrig S., Cole T., Niemann S., Munnich A.,
Gaultier C., Lyonnet S., Amiel J.;
"PHOX2B genotype allows for prediction of tumor risk in congenital
central hypoventilation syndrome.";
Am. J. Hum. Genet. 76:421-426(2005).
[9]
ERRATUM.
Trochet D., O'Brien L.M., Gozal D., Trang H., Nordenskjoeld A.,
Laudier B., Svensson P.-J., Uhrig S., Cole T., Niemann S., Munnich A.,
Gaultier C., Lyonnet S., Amiel J.;
Am. J. Hum. Genet. 76:715-715(2002).
[10]
VARIANT ASP-197, AND NEUROBLASTOMA SUSCEPTIBILITY.
PubMed=16691592; DOI=10.1002/ajmg.a.31278;
McConville C., Reid S., Baskcomb L., Douglas J., Rahman N.;
"PHOX2B analysis in non-syndromic neuroblastoma cases shows novel
mutations and genotype-phenotype associations.";
Am. J. Med. Genet. A 140:1297-1301(2006).
-!- FUNCTION: Involved in the development of several major
noradrenergic neuron populations, including the locus coeruleus.
Transcription factor which could determine a neurotransmitter
phenotype in vertebrates. Enhances second-messenger-mediated
activation of the dopamine beta-hydrolase and c-fos promoters, and
of several enhancers including cAMP-response element and serum-
response element.
-!- SUBUNIT: Interacts with TRIM11. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108}.
-!- TISSUE SPECIFICITY: Expressed in neuroblastoma, brain and adrenal
gland.
-!- DISEASE: Congenital central hypoventilation syndrome (CCHS)
[MIM:209880]: Rare disorder characterized by abnormal control of
respiration in the absence of neuromuscular or lung disease, or an
identifiable brain stem lesion. A deficiency in autonomic control
of respiration results in inadequate or negligible ventilatory and
arousal responses to hypercapnia and hypoxemia.
{ECO:0000269|PubMed:12640453, ECO:0000269|PubMed:14566559,
ECO:0000269|PubMed:15657873}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Neuroblastoma 2 (NBLST2) [MIM:613013]: A common neoplasm
of early childhood arising from embryonic cells that form the
primitive neural crest and give rise to the adrenal medulla and
the sympathetic nervous system. {ECO:0000305|PubMed:15024693}.
Note=Disease susceptibility is associated with variations
affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; D82344; BAA11555.1; -; mRNA.
EMBL; AF117979; AAD26698.1; -; Genomic_DNA.
EMBL; AB015671; BAA82670.1; -; Genomic_DNA.
EMBL; BC017199; AAH17199.1; -; mRNA.
CCDS; CCDS3463.1; -.
PIR; JC5273; JC5273.
RefSeq; NP_003915.2; NM_003924.3.
UniGene; Hs.87202; -.
ProteinModelPortal; Q99453; -.
SMR; Q99453; -.
BioGrid; 114443; 1.
STRING; 9606.ENSP00000226382; -.
iPTMnet; Q99453; -.
PhosphoSitePlus; Q99453; -.
BioMuta; PHOX2B; -.
DMDM; 116242712; -.
MaxQB; Q99453; -.
PaxDb; Q99453; -.
PeptideAtlas; Q99453; -.
PRIDE; Q99453; -.
Ensembl; ENST00000226382; ENSP00000226382; ENSG00000109132.
GeneID; 8929; -.
KEGG; hsa:8929; -.
UCSC; uc003gwf.4; human.
CTD; 8929; -.
DisGeNET; 8929; -.
EuPathDB; HostDB:ENSG00000109132.6; -.
GeneCards; PHOX2B; -.
GeneReviews; PHOX2B; -.
H-InvDB; HIX0120072; -.
HGNC; HGNC:9143; PHOX2B.
HPA; HPA074325; -.
MalaCards; PHOX2B; -.
MIM; 209880; phenotype.
MIM; 603851; gene.
MIM; 613013; phenotype.
neXtProt; NX_Q99453; -.
OpenTargets; ENSG00000109132; -.
Orphanet; 99803; Haddad syndrome.
Orphanet; 635; Neuroblastoma.
Orphanet; 661; Ondine syndrome.
PharmGKB; PA33467; -.
eggNOG; KOG0484; Eukaryota.
eggNOG; ENOG4111YNP; LUCA.
GeneTree; ENSGT00900000140809; -.
HOGENOM; HOG000013060; -.
HOVERGEN; HBG094678; -.
InParanoid; Q99453; -.
KO; K09330; -.
OMA; QGWASAP; -.
OrthoDB; EOG091G0YX9; -.
PhylomeDB; Q99453; -.
TreeFam; TF351612; -.
SignaLink; Q99453; -.
SIGNOR; Q99453; -.
GeneWiki; PHOX2B; -.
GenomeRNAi; 8929; -.
PRO; PR:Q99453; -.
Proteomes; UP000005640; Chromosome 4.
Bgee; ENSG00000109132; -.
CleanEx; HS_PHOX2B; -.
Genevisible; Q99453; HS.
GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB.
GO; GO:0048483; P:autonomic nervous system development; IMP:BHF-UCL.
GO; GO:0003360; P:brainstem development; IEP:BHF-UCL.
GO; GO:0021533; P:cell differentiation in hindbrain; ISS:BHF-UCL.
GO; GO:0071773; P:cellular response to BMP stimulus; ISS:BHF-UCL.
GO; GO:0071542; P:dopaminergic neuron differentiation; ISS:BHF-UCL.
GO; GO:0048894; P:efferent axon development in a lateral line nerve; ISS:BHF-UCL.
GO; GO:0048484; P:enteric nervous system development; IEP:BHF-UCL.
GO; GO:0010001; P:glial cell differentiation; ISS:BHF-UCL.
GO; GO:0021934; P:hindbrain tangential cell migration; ISS:BHF-UCL.
GO; GO:0048839; P:inner ear development; ISS:BHF-UCL.
GO; GO:0021723; P:medullary reticular formation development; ISS:BHF-UCL.
GO; GO:0071157; P:negative regulation of cell cycle arrest; ISS:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl.
GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
GO; GO:1901166; P:neural crest cell migration involved in autonomic nervous system development; ISS:BHF-UCL.
GO; GO:0001764; P:neuron migration; ISS:BHF-UCL.
GO; GO:0003358; P:noradrenergic neuron development; ISS:UniProtKB.
GO; GO:0003357; P:noradrenergic neuron differentiation; ISS:BHF-UCL.
GO; GO:0048486; P:parasympathetic nervous system development; ISS:BHF-UCL.
GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISS:UniProtKB.
GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
GO; GO:0002087; P:regulation of respiratory gaseous exchange by neurological system process; ISS:BHF-UCL.
GO; GO:0060541; P:respiratory system development; ISS:BHF-UCL.
GO; GO:0061452; P:retrotrapezoid nucleus neuron differentiation; ISS:BHF-UCL.
GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
GO; GO:0061549; P:sympathetic ganglion development; ISS:UniProtKB.
GO; GO:0048485; P:sympathetic nervous system development; ISS:BHF-UCL.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
Pfam; PF00046; Homeobox; 1.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Activator; Complete proteome; Developmental protein; Disease mutation;
DNA-binding; Homeobox; Nucleus; Reference proteome; Transcription;
Transcription regulation; Triplet repeat expansion.
CHAIN 1 314 Paired mesoderm homeobox protein 2B.
/FTId=PRO_0000049262.
DNA_BIND 98 157 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
COMPBIAS 159 167 Poly-Ala.
COMPBIAS 212 217 Poly-Gly.
COMPBIAS 241 260 Poly-Ala.
VARIANT 100 100 R -> L (confers susceptibility to
neuroblastoma; found as germline mutation
in a neuroblastoma family;
dbSNP:rs104893855).
{ECO:0000269|PubMed:15024693}.
/FTId=VAR_026969.
VARIANT 141 141 R -> G (in dbSNP:rs28939716).
{ECO:0000269|PubMed:15024693}.
/FTId=VAR_026970.
VARIANT 141 141 R -> Q (in CCHS).
{ECO:0000269|PubMed:15657873}.
/FTId=VAR_046900.
VARIANT 143 143 Q -> R (in CCHS).
{ECO:0000269|PubMed:15657873}.
/FTId=VAR_046901.
VARIANT 197 197 G -> D (confers susceptibility to
neuroblastoma; dbSNP:rs104893856).
{ECO:0000269|PubMed:16691592}.
/FTId=VAR_046902.
VARIANT 241 241 A -> AAAAAAAAAAA (in CCHS).
{ECO:0000269|PubMed:14566559}.
/FTId=VAR_018257.
VARIANT 254 258 Missing. {ECO:0000269|PubMed:14566559}.
/FTId=VAR_018258.
VARIANT 255 259 Missing. {ECO:0000269|PubMed:14566559}.
/FTId=VAR_018259.
CONFLICT 292 292 A -> G (in Ref. 1; BAA11555, 2; AAD26698
and 3; BAA82670). {ECO:0000305}.
SEQUENCE 314 AA; 31621 MW; 40737F71948B595A CRC64;
MYKMEYSYLN SSAYESCMAG MDTSSLASAY ADFSSCSQAS GFQYNPIRTT FGATSGCPSL
TPGSCSLGTL RDHQSSPYAA VPYKLFTDHG GLNEKRKQRR IRTTFTSAQL KELERVFAET
HYPDIYTREE LALKIDLTEA RVQVWFQNRR AKFRKQERAA AAAAAAAKNG SSGKKSDSSR
DDESKEAKST DPDSTGGPGP NPNPTPSCGA NGGGGGGPSP AGAPGAAGPG GPGGEPGKGG
AAAAAAAAAA AAAAAAAAAA GGLAAAGGPG QGWAPGPGPI TSIPDSLGGP FASVLSSLQR
PNGAKAALVK SSMF


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